Clinical studies indicate a role of allogeneic hematopoietic cell transplantation (alloHCT) for patients with refractory or recurrent B-cell lymphoma (BCL) indicative of a graft-versus-tumor effect. However, the relevance of local immunosuppression in the BCL microenvironment by donor-derived regulatory T cells (Treg) after alloHCT is unclear. Therefore, we studied Treg recruitment after alloHCT in different murine BCL models and the impact of lymphoma-derived chemoattractive signals. Luciferase transgenic Tregs accumulated in murine BCL microenvironment and microarray-based analysis of BCL tissues revealed increased expression of CXCL9, CXCL10, and CXCL12. In vivo blocking identified the CXCR4/CXCL12 axis as being critical for Treg attraction toward BCL. In contrast to Tregs, effector T cells displayed low levels of CXCR4 and were not affected by the pharmacologic blockade. Most important, blocking CXCR4 not only reduced Treg migration toward tumor tissue but also enhanced antitumor responses after alloHCT. CXCL12 production was dependent on antigenpresenting cells (APC) located in the lymphoma microenvironment, and their diphtheria-toxin receptor (DTR)-based depletion in CD11c.DTR-Tg mice significantly reduced Treg accumulation within BCL tissue. CXCL12 was also detected in human diffuse, large BCL tissues indicative of its potential clinical relevance.In conclusion, we demonstrate that Tregs are recruited toward BCL after alloHCT by infiltrating host APCs in a CXCL12-dependent fashion. Blocking CXCR4 enhanced antitumor effects and prolonged survival of tumor-bearing mice by reducing local Treg accumulation, indicating that CXCR4 is a potential target to interfere with tumor escape after alloHCT.
Iron ore sintering is an important source of "dioxins", polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This paper reports on attempts to identify materials, conditions, and mechanisms responsible for PCDD/F formation (i) by investigating salient properties of ores (viz., with respect to oxidation, condensation, and chlorination of model organics) and (ii) by mimicking the industrial process on a microscale with real-life materials. Principles of Design of Experiments (DOE) are employed. The reactivities of iron ores differ greatly. Limonite/goethite "soft" ore is a very active oxidation catalyst (e.g., for benzene and phenol), a property that may be useful in cleaning up crude sintering process offgases, whereas hematite/magnetite "hard" ore is not. The latter, however strongly promotes condensation of phenol to dibenzofuran. A newly built lab-microscale sintering facility could satisfactorily imitate the large-scale process, in part or as a whole. Results obtained with realistic feed mixtures point at dioxin formation in the sinter bed at levels significant enough to explain a major part of the outputs observed in the real-life process. With approximately 8 ppm (wt) of chloride added as NaCl, the PCDD/F output doubled, but with the same proportion of chlorine administered as C2Cl4, the dioxin output was over 2 orders of magnitude larger. The use of process reverts, etc. containing chlorinated organics should therefore be avoided. PCDD/F congener patterns are also reported and compared with those observed in practice.
Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.
Abstract. During endoscopic operations the surgeon works without direct visual contact to the operation area. The image of the operation situs is displayed on a monitor. Currently, only hardware based image enhancement methods are used (e. g., white balance) and often only once at the beginning of an operation. In this contribution we describe a system for real-time endoscopic image enhancement: a typical video-endoscopic system was extended by a computer and a second monitor. Thus the enhanced and the original image can be displayed at the same time. The implemented image enhancement methods (temporal filtering, undistortion and color normalization) were evaluated by 14 surgeons and the results showed that the enhanced images were preferred. The system was already used during a real operation.
Writing learning journals is a powerful tool to integrate self-regulated learning in classrooms. However, to exploit the full potential of journal writing, instructional support is needed that addresses the students' deficits in the use of self-regulated learning strategies. A promising means to foster learning strategies in learning journals is the provision of solved example problems along with prompts. In a quasiexperimental field study, we provided fifth-grade students (N = 48) with solved example problems along with prompts either right from the beginning of writing their journals or after they had already written two learning journal entries. We found that the provision of solved example problems along with prompts right from the beginning of the journal writing process fostered the quality of both cognitive and metacognitive strategies and conceptual knowledge in the initial phase. The delayed provision of solved example problems after an initial phase of journal writing yielded a detrimental effect on the quality of cognitive strategies and a beneficial effect on the quality of metacognitive strategies. In sum, our results suggest that the provision of solved example problems along with prompts right from the beginning of journal writing can effectively support fifth-grade students in overcoming deficits in the use of self-regulated learning strategies.
Endoscopic sympathetic block (ESB) is used as a treatment of excessive palmar sweating. In a prospective study we compared the effect of ESB at the level of the second (T2) and fourth thoracic ganglion (T4) on vasoconstriction and sweating of the hands. Sympathetic vasoconstriction was measured by computerassisted infrared thermography following ice water immersion of the hands in 22 hyperhidrosis patients before, two days and 3 months post op. In addition, palmar sweating before and 3 months post op was assessed by sudometry. After ESB the rewarming was accelerated in both T2 and T4 patients, but was significantly slower in the T4 group. Three months postoperatively rewarming had returned to the preoperative pattern in T4 patients but was still significantly faster in the T2 group. These effects were more pronounced in the fingertips than the hand dorsum. Sudomotor function was blocked in all T2 patients but had relapsed in 2 patients in the T4 group. Two T4 patients had not shown an effect on sudomotor function postoperatively. The normalization of rewarming kinetics may be explained by remaining fibers, denervation hypersensitivity or stimulation of catecholamine receptors, or neuronal reorganization. The effect of ESB T4 on sudomotor function has to be proven.
Forearm skin perfusion is increased after ETSC on the T2 or T3 level indicating decreased sympathetic activity while BK-induced protein extravasation was increased. These results show that preganglionic sympathectomy does not diminish bradykinin-induced protein extravasation as found for postganglionic sympathectomy in rats.
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